Idiotype profile of an immune response. II. Reversal of the relative dominance of major and minor cross-reactive idiotypes in arsonate-specific T-independent responses.

Abstract

The antibody (Ab) l response of A/J mice to the p-azobenzenearsonate (ABA) hapten includes a substantial cross-reactive idiotypic (CRI or IdX) component (1). Serological (2) and amino acid sequence (3-5) studies on ABA-specific monoclonal Abs (mAb or HP) produced by hybridomas (derived using A/J ABAhyperimmune splenocytes) have indicated that all the HP examined are unique. However, CRI + HP can be shown to share one or more conserved IdX determinant(s) (6). Despite the microheterogeneity of the family of molecules bearing the major CRI, it appears that the heavy chain variable (VH), and probably the light chain variable (VL) regions are each encoded by a single germline gene that undergoes somatic variation (7,8). Recently, Milner and Capra (9) showed that the available N-terminal VH sequences could be classed into three distinct VH homology families, which might be termed: (a) the CRIA group (prototypes HP: R16.7, 93G7 [2], and 36-65 [4]); (b) the CRIc, family (prototypes: HP 92D5 [9] and 36-60 [10]); and, (c) the 96B8 family, which has not previously been serologically detected as a distinct IdX entity in the Ab response. It seems likely that these homology families result from the expression of at least three different Vu genes present in the strain A germline.A comparable complexity was recently demonstrated by Brown et al. (11) to exist at the serological level among induced anti-ABA Abs of A/J mice. Utilization of an anti-Id serum, prepared against HP R 16.7, which had previously been shown to bear virtually all of the major CRI determinants found among induced

Influence of <i>xid</i> on Anti-Azophenylarsonate (Ar) Antibody Responses of (CBA/N × A/J)F₁ Mice: Differential Idotype Expression Induced by Only One of Two Ar Antigens

“…The re quired resources for an equally large analysis of such ANFi mice were not available. In two earlier studies, however, no significant differences in response mag nitude or CRIa content were noted between ANF| males and NAFi females in responses elicited by KLH-Ar [13] or BA-Ar [12]. It is, therefore, doubtful that sex differences acount for the differential aspects of the anti-Ar responses noted in this report.…”

“…Previously, it was proposed [12], based on indirect evidence, that most virgin anti-Ar precursors in the Lyb 3,5+ subset were CRIA+ while Id expres sion in the Lyb 3,5" subpopulation was generally lower and more variable. The recent finding [13] that a TD type II [23] form of Ar, which addresses only the Lyb 3,5 + B cell subset, and elicits a highly CRIA-dominant Ab response in strain A mice would seem to be in line with this hypothesis, although other explana tions for this observation are possible.…”

“…In the anti-p-azophenylarsonate (Ar)-CRI system in A strain mice, two apparently contradictory reports have appeared. Conger et al [12] reported that male (CBA/N x A/J)F| (=NAF|) mice, which express xid, showed a relative depression, but not absence of CRI+ plaque-forming cells (PFC) in PFC responses induced by Ar coupled to Brucella abortus (BA). However, Woodland and Huber [13], using serologi cal methodology, found no significant difference in CRIa expression between NAF| female and male mice in anti-Ar responses elicited by KLH-Ar.…”

Assays for B Lymphocyte Function

“…Antigens such as polyvinyl pyrrolidone, pneumococcal polysaccharides or haptens such as arsonate or 4-hydroxy 5-iodo 3-nitrophenyl, phosphoryl choline have also been conjugated to SRBC and used in PFC assays (Conger et al, 1983;Cronkhite et al, 1984;Garg et al, 1994;Goud et al, 1992;Swenson et al, 1997). 6.…”

“…Generally, trinitrophenyl groups have been used as haptens in many systems since the PFC assays are well suited for this hapten. Some of the other haptens that can be used are nitroiodophenyl (NIP), nitrophenyl (NP), phosphoryl choline, and arsonate (Conger et al, 1983;Cronkhite et al, 1984;Garg et al, 1994;Goud et al, 1992;Swenson et al, 1997).…”